Clinical and histopathological characterization of metastatic lobular breast cancer: lessons learned from post-mortem tissue donation programs

While primary invasive lobular carcinoma (ILC) is well characterized, metastatic ILC remains understudied. Within the post-mortem tissue donation programs, UPTIDER (Belgium) and Hope for Others (USA), we first aimed to explore intra-patient heterogeneity of key prognostic and predictive markers (stromal tumor-infiltrating lymphocytes (sTIL), estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and KI67). Secondly, we compared detection of the metastases by pathology on autopsy samples versus pre-mortem imaging. In total, 306 metastases from 12 patients were collected at autopsy (median: 27 per patient). Both primary tumors (n = 15) and metastases (n = 232) had low sTIL levels, with a median of 2% (range: 0.67-6.67%) and 0.67% (range: 0-13.33%), respectively. Regression models showed lower ER- and PR-expression in metastases (respectively, n = 265 and n = 64) compared to primary tumors (both p < 0.01). KI67 was significantly higher in metastases (n = 262, p = 0.02). HER2-low metastases were found in all but one patient although in varying proportion of metastases (range: 7.5-100%). Central radiology and pathology review had a median concordance of 78% at organ level (range: 33.33-100%) and 71% at patient level (range: 55.88-85.29%). Our findings suggest that a single metastatic biopsy has great limitations to guide treatment and that more adequate methods are needed to detect and monitor ILC metastases.